Spherical crystal ergosterol and preparation method thereof

Abstract

The invention belongs to the technical field of medicinal chemistry, and particularly discloses ergosterol of a spherical crystal and a preparation method thereof. The preparation method comprises the following steps: heating and mixing ergosterol and ethyl acetate to obtain a mixed solution; and cooling the obtained mixed solution to a crystal growing temperature, growing the crystal, and filtering after the crystal growing is finished, so as to obtain the ergosterol of a spherical crystal. Compared with traditional flaky or needle-shaped crystals and spherical crystals prepared by other methods in the market, the ergosterol of the spherical crystal prepared by the invention has good fluidity, and a series of problems caused by material addition can be greatly improved, so that the industrial production cost is reduced, and the economic benefit is increased.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical chemistry, and in particular to spherical crystal ergosterol and a preparation method thereof. Background Art

[0002] Ergosterol, also known as ergosterol, is white or colorless shiny small leaf crystals or white crystalline powder. Ergosterol not only has unique physiological effects, but is also widely used in drug development.

[0003] The structural formula of ergosterol:

[0004] Ergosterol can enhance the body's ability to resist disease and is an important source of fat-soluble vitamin D2, with significant antibacterial and anti-tumor effects. The converted vitamin D2 can be added to feed as a feed additive to increase the egg production and hatching rate of livestock and poultry. Ergosterol can also be used as an important pharmaceutical chemical raw material for the production of steroid drugs such as "cortisone" and "hormone progesterone".

[0005] Ergosterol can also be used to synthesize brassinolide, which, as a plant growth regulator, has excellent market prospects. The number of product registrations has more than doubled compared to a few years ago, and has great market potential. At present, the global pesticide market sales are basically stable at around US$65 billion, of which plant growth regulators account for about 3%. From a global perspective, in recent years, in the market environment where other pesticides have developed slowly, the plant growth regulator market has maintained a sustained and stable growth trend.

[0006] The common method of solid feeding in industry is to use a bucket-type solid feeder for feeding. However, in the industrial feeding process, traditional flake or needle-shaped crystal drugs have poor fluidity and are prone to accumulation, resulting in poor equipment operation and serious impact on production. The fluidity of spherical crystals is better than that of non-spherical crystals, which makes the mixing and processing process more uniform and controllable.

[0007] H Kawachi's team used a method of adding hexane to water to crystallize ergosterol-like spherical precipitates - cauliflower-like precipitates. Scanning electron microscopy showed that the spherical precipitates had cracks, the surface was covered with small and thin needle-shaped monohydrate crystals, and the interior was smooth solid. However, the spherical precipitates prepared by this method were not smooth on the surface, had crack walls, incomplete structural morphology, and poor fluidity.

[0008] Therefore, how to provide a spherical crystal of ergosterol and a preparation method thereof, improve the crystal morphology of ergosterol, increase product fluidity, and avoid material accumulation are difficult problems to be solved in the art. Summary of the invention

[0009] In view of this, the present invention provides a spherical crystal ergosterol and a preparation method thereof, so as to solve the problem that the existing ergosterol of flake crystals or needle crystals has the problem of unsmooth feeding, and the problem that the ergosterol prepared by the existing spherical crystal ergosterol preparation method has low sphericity, rough surface, crack wall, incomplete structure and morphology, and poor fluidity.

[0010] In order to achieve the above object, the present invention adopts the following technical solution:

[0011] A method for preparing spherical crystal ergosterol, characterized in that it comprises the following steps:

[0012] 1) heating and mixing ergosterol and ethyl acetate to obtain a mixed solution;

[0013] 2) The mixed solution obtained in step 1) is cooled to a crystal growing temperature, and crystal growing is performed. After the crystal growing is completed, the mixed solution is filtered to obtain spherical crystals of ergosterol.

[0014] Preferably, the mass volume ratio of ergosterol to ethyl acetate is 0.35 g: 2-5 mL.

[0015] Preferably, the heating and mixing temperature is 75 to 80° C., and the heating and mixing time is 0.5 to 1 h.

[0016] Preferably, the crystal growing temperature is 65-75° C., and the crystal growing time is 3-8 hours.

[0017] Preferably, the filtration temperature in step 2) is the same as the crystal growing temperature.

[0018] Preferably, the ergosterol in step 1) comprises ergosterol in the form of plate-like crystals and / or ergosterol in the form of needle-like crystals.

[0019] Another object of the present invention is to provide spherical crystal ergosterol prepared by the preparation method.

[0020] It can be seen from the above technical solutions that, compared with the prior art, the present invention has the following beneficial effects:

[0021] 1. The spherical crystals of ergosterol prepared by the present invention have good fluidity compared with the traditional flake or needle-shaped crystals on the market and the spherical crystals prepared by the existing method, and can greatly improve a series of problems caused by adding materials (including problems such as blockage and damage of equipment pipelines caused by improper adding materials, which greatly increases the equipment maintenance and cleaning costs, and increases the time and economic costs in the production process), thereby reducing industrial production costs and increasing economic benefits.

[0022] 2. Compared with the existing method of preparing spherical ergosterol using n-hexane-water, the ethyl acetate solvent has lower cost and can bring better economic benefits. In addition, the spherical crystals of ergosterol prepared by the present invention have higher sphericity, smoother surface, more complete structure and better macroscopic fluidity. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying creative work.

[0024] Figure 1 This is a SEM image of ergosterol in spherical crystals of Example 1 of the present invention magnified 8000 times;

[0025] Figure 2 This is a SEM image of the spherical crystals of ergosterol in Example 1 of the present invention magnified 10,000 times;

[0026] Figure 3 The XRD pattern of ergosterol in spherical crystals prepared in Example 1 of the present invention;

[0027] Figure 4 This is a SEM image of ergosterol crystals prepared in Comparative Example 1 of the present invention magnified 840 times;

[0028] Figure 5 This is a 100-fold magnified optical microscope image of ergosterol crystals obtained in Comparative Example 2-1 of the present invention;

[0029] Figure 6 This is a 100-fold magnified optical microscope image of ergosterol crystals obtained in Comparative Example 2-2 of the present invention;

[0030] Figure 7 This is a 100-fold magnified optical microscope image of ergosterol crystals obtained in Comparative Example 2-3 of the present invention;

[0031] Figure 8 This is a 100-fold magnified optical microscope image of ergosterol crystals obtained in Comparative Examples 2-4 of the present invention;

[0032] Fig. 9 This is a 100-fold magnified optical microscope image of ergosterol crystals obtained in Comparative Examples 2-5 of the present invention;

[0033] Fig.10 This is a 100-fold magnified optical microscope image of ergosterol crystals obtained in Comparative Examples 2-6 of the present invention;

[0034] Fig.11This is a 100-fold magnified optical microscope image of ergosterol crystals obtained in Comparative Examples 2-7 of the present invention;

[0035] Fig.12 This is a 100-fold magnified optical microscope image of ergosterol crystals obtained in Comparative Example 2-8 of the present invention;

[0036] Fig.13 This is a 100-fold magnified optical microscope image of ergosterol crystals obtained in Comparative Example 2-9 of the present invention;

[0037] Fig.14 This is a SEM image of ergosterol crystals prepared in Comparative Example 3-1 of the present invention;

[0038] Fig.15 This is a SEM image of ergosterol crystals prepared in Comparative Example 3-2 of the present invention. DETAILED DESCRIPTION

[0039] The present invention provides a method for preparing spherical crystal ergosterol, which is characterized by comprising the following steps:

[0040] 1) heating and mixing ergosterol and ethyl acetate to obtain a mixed solution;

[0041] 2) The mixed solution obtained in step 1) is cooled to a crystal growing temperature, and crystal growing is performed. After the crystal growing is completed, the mixed solution is filtered to obtain spherical crystals of ergosterol.

[0042] In the present invention, the mass volume ratio of ergosterol to ethyl acetate is 0.35 g: 2 to 5 mL, preferably 0.35 g: 2 to 4 mL, and more preferably 0.35 g: 2 to 3 mL.

[0043] In the present invention, the heating and mixing temperature is 75-80°C, specifically 76°C, 77°C, 78°C, 79°C; the heating and mixing time is 0.5-1h, specifically 0.6h, 0.7h, 0.8h, 0.9h.

[0044] In the present invention, the crystal growing temperature is 65-75°C, specifically 66°C, 68°C, 70°C, 72°C, 74°C; the crystal growing time is 3-8h, specifically 4h, 5h, 6h, 7h.

[0045] In the present invention, ergosterol is completely dissolved during the dissolution process. When the temperature is lowered to the crystal growing temperature, crystals begin to precipitate. This is the crystal nucleation stage. When crystal growing is carried out at this temperature, it can be observed that the amount of crystal precipitation in the first 1 hour is trace. As the crystal growing time increases, the amount of crystal precipitation gradually increases, and the precipitation reaches the maximum when the crystal growing time is 5 hours.

[0046] In the present invention, the filtration temperature in step 2) is the same as the crystal growing temperature.

[0047] In the present invention, the cooling rate to the crystal growing temperature in step 2) is preferably 4-8 min / °C, specifically 4.5 min / °C, 5 min / °C, 5.5 min / °C, 6 min / °C, 6.5 min / °C, 7 min / °C, 7.5 min / °C; the most preferred rate is 6 min / °C.

[0048] In the present invention, the ergosterol in step 1) includes ergosterol in the form of plate-like crystals and / or ergosterol in the form of needle-like crystals.

[0049] The invention also provides spherical crystal ergosterol prepared by the preparation method.

[0050] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0051] Example 1

[0052] Add 1.75 g of ergosterol (ergosterol in the form of flaky crystals) to 10 mL of ethyl acetate, start reflux heating at 80°C, dissolve for 1 hour to obtain a mixed solution (ergosterol is completely dissolved), cool the temperature to 70°C at a cooling rate of 6 min / °C, grow the crystals for 5 hours, filter while hot at this temperature, and rotary evaporate to dryness to obtain spherical crystals of ergosterol.

[0053] Example 2

[0054] Add 1.75 g of ergosterol (ergosterol in the form of flaky crystals) to 15 mL of ethyl acetate, start reflux heating at 75 ° C, dissolve for 1 hour to obtain a mixed solution (ergosterol is completely dissolved), cool the temperature to 65 ° C at a cooling rate of 6 min / ° C, grow the crystals for 3 hours, filter while hot at this temperature, and rotary evaporate to dryness to obtain spherical crystals of ergosterol.

[0055] Example 3

[0056] Add 1.75 g of ergosterol (needle-shaped crystals of ergosterol) to 25 mL of ethyl acetate, start reflux heating at 80°C, dissolve for 0.6 h to obtain a mixed solution (ergosterol is completely dissolved), cool to 75°C at a cooling rate of 6 min / °C, grow crystals for 8 h, filter while hot at this temperature, and rotary evaporate to dryness to obtain spherical crystals of ergosterol.

[0057] Experimental Example 1

[0058] The spherical crystals of ergosterol prepared in Example 1 were observed using a scanning electron microscope. The results were as follows Figures 1-2 As shown ( Figure 1 The SEM image is magnified 8000 times; Figure 2 (SEM image magnified 10000 times) Figures 1-2 It can be seen that the spherical crystals of ergosterol are complete in shape, with no cracks on the surface and are relatively smooth.

[0059] The plate-like ergosterol raw material in Example 1 was used as a control group (referred to as control), and the spherical ergosterol prepared in Example 1 was used as an experimental group (referred to as spherical crystals) for X-ray diffraction (using Cu-Kα radiation in the range of 2θ, the range is 2-50°, and the scanning speed is 8° / min). The test results are as follows: Figure 3 As shown. Figure 3 It can be seen that the XPRD spectrum of ergosterol in spherical crystals expressed at 2θ angles has the following characteristic peaks: 2.28±0.2°, 4.67±0.2°, 6.92±0.2°, 9.69±0.2°, 12.09±0.2°, 14.89±0.2°, 15.48±0.2°, 19.29±0.2°, 22.86±0.2°; The XPRD spectrum of ergosterol (control) expressed at 2θ angle has the following characteristic peaks: 2.42±0.2°, 4.91±0.2°, 7.37±0.2°, 10.01±0.2°, 12.47±0.2°, 15.03±0.2°, 16.04±0.2°, 17.60±0.2°, 19.68±0.2°, 22.73±0.2°. The spherical crystals of ergosterol prepared by the present invention are compared with the flaky crystals of ergosterol sold on the market, and the peaks of the two are similar, but the peaks of the XRD pattern of the spherical crystals prepared by the present invention are wider.

[0060] Carr Index

[0061] Bulk density (bulk density): refers to the mass of matter contained in unit volume in a natural stacking state without compaction or compression. It is a way of expressing the density of materials, a characterization of materials, granular materials, etc., and the unit is (g / mL).

[0062] Bulk density test: First, clean the 10mL measuring cylinder thoroughly, then place the measuring cylinder in an oven for drying until the measuring cylinder reaches a constant weight, which is recorded as B. Place the ergosterol sample 3 cm from the top of the measuring cylinder, and let the sample fall naturally into the measuring cylinder through a funnel, ensuring that the height of the sample accumulation exceeds the wall of the measuring cylinder. Use a medicine spoon to remove the excess part exceeding the top of the measuring cylinder, and weigh the ergosterol sample to four decimal places (0.1 mg), which is recorded as A.

[0063] Bulk density calculation formula:

[0064] X=(AB) / V

[0065] Where:

[0066] X——bulk density of the sample (g / mL)

[0067] V——Volume of sample (mL)

[0068] A——Mass of measuring cylinder and sample (g)

[0069] B——mass of the measuring cylinder (g)

[0070] Tap density: repeatedly oscillate the loose density measuring cylinder until the volume of the powder in the measuring cylinder no longer decreases, continue to add sample until the height of the sample accumulation exceeds the wall of the measuring cylinder, use a medicine spoon to remove the excess part exceeding the top of the measuring cylinder, and weigh the ergosterol sample to four decimal places (0.1 mg), which is recorded as C.

[0071] The calculation formula of tap density is:

[0072] Y=(CB) / V

[0073] Where:

[0074] Y——tapped density of the sample (g / mL)

[0075] V——Volume of sample (mL)

[0076] C——Mass of measuring cylinder and sample (g)

[0077] B——mass of the measuring cylinder (g)

[0078] Carr's index = (tapped density - bulk density) / tapped density. Carr's index reflects the quality of fluidity. The smaller the value, the better the surface fluidity.

[0079] According to the above method, the spherical crystals of ergosterol prepared in Example 1 (referred to as Example 1) and the flaky crystals of ergosterol raw material (referred to as control) were tested respectively. The test results are shown in Table 1.

[0080] Table 1 Test results of bulk density, tap density and Carr index

[0081]

[0082] As shown in Table 1, the spherical crystals of ergosterol prepared by the present invention have a smaller Carr coefficient and better fluidity than the flake ergosterol products (raw materials) available on the market.

[0083] Comparative Example 1

[0084] Using the crystal preparation method of H Kawachi's team, 0.18 g of ergosterol was added to 50 mL of hexane containing 185 ppm of water, the temperature was raised to 60°C, heated and stirred for 3 hours, and the ergosterol was completely dissolved. The temperature was then lowered to 10°C at a cooling rate of 5 min / °C, filtered at this temperature, and dried at room temperature to obtain ergosterol crystals.

[0085] The obtained ergosterol crystals were observed using a scanning electron microscope, and the 840-fold magnification result was as follows: Figure 4 As shown, through Figure 4 It can be seen that the "cauliflower-like precipitate" prepared by this method has an uneven surface, cracked walls, and an incomplete structural morphology.

[0086] The bulk density, tap density and Carr's index of Comparative Example 1 were tested according to the method of Experimental Example 1. The test results are shown in Table 2.

[0087] Table 2 Comparative Example 1 Bulk density, tap density, Carr index test results

[0088]

[0089] It can be seen from Table 2 that, compared with the ergosterol crystals prepared by the H Kawachi team, the ergosterol spherical crystals prepared by the present invention have a smaller Carr coefficient and better fluidity.

[0090] Comparative Example 2

[0091] The ethyl acetate in Example 1 was replaced with methanol, ethanol, isopropanol, n-propanol, n-butanol, tert-butanol, n-pentanol, toluene, and acetone in equal volumes; and the corresponding parameters were adjusted according to the solubility characteristics of ergosterol in different solvents. Comparative Examples 2-1, 2-2, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, and 2-9 were obtained respectively.

[0092] Comparative Example 2-1

[0093] Add 0.059 g of ergosterol (ergosterol in the form of flaky crystals) to 10 mL of methanol, start reflux heating at 70°C, dissolve for 1 hour to obtain a mixed solution (ergosterol is completely dissolved), cool the temperature to 40°C at a cooling rate of 6 min / °C, grow the crystals for 5 hours, filter at the same temperature, and rotary evaporate to dryness to obtain ergosterol in the form of flaky crystals.

[0094] The obtained ergosterol crystals were observed under an optical microscope. Figure 5As shown, through Figure 5 It can be seen that the crystallization of ergosterol in methanol produces flaky crystals rather than spherical crystals.

[0095] Comparative Example 2-2

[0096] Add 0.125 g of ergosterol (ergosterol in the form of flaky crystals) to 10 mL of ethanol, start reflux heating at 80°C, dissolve for 1 hour to obtain a mixed solution (ergosterol is completely dissolved), cool the temperature to 40°C at a cooling rate of 6 min / °C, grow the crystals for 5 hours, filter at the same temperature, and rotary evaporate to dryness to obtain ergosterol in the form of flaky crystals.

[0097] The obtained ergosterol crystals were observed under an optical microscope. Figure 6 As shown, through Figure 6 It can be seen that the crystallization of ergosterol in ethanol produces flaky crystals rather than spherical crystals.

[0098] Comparative Examples 2-3

[0099] Add 0.25 g of ergosterol (ergosterol in the form of flaky crystals) to 10 mL of isopropanol, start reflux heating at 85°C, dissolve for 1 hour to obtain a mixed solution (ergosterol is completely dissolved), cool the temperature to 40°C at a cooling rate of 6 min / °C, grow the crystals for 5 hours, filter at the same temperature, and rotary evaporate to dryness to obtain ergosterol in the form of flaky crystals.

[0100] The obtained ergosterol crystals were observed under an optical microscope. Figure 7 As shown, through Figure 7 It can be seen that the crystallization of ergosterol in isopropanol produces flaky crystals, rather than spherical crystals.

[0101] Comparative Examples 2-4

[0102] Add 0.5 g of ergosterol (ergosterol in the form of flaky crystals) to 10 mL of n-propanol, start reflux heating at 80°C, dissolve for 1 hour to obtain a mixed solution (ergosterol is completely dissolved), cool the temperature to 45°C at a cooling rate of 6 min / °C, grow the crystals for 5 hours, filter at the same temperature, and rotary evaporate to dryness to obtain ergosterol in the form of flaky crystals.

[0103] The obtained ergosterol crystals were observed under an optical microscope. Figure 8 As shown, through Figure 8 It can be seen that the crystallization of ergosterol in n-propanol produces flaky crystals rather than spherical crystals.

[0104] Comparative Examples 2-5

[0105] Add 0.7 g of ergosterol (ergosterol in the form of flaky crystals) to 10 mL of n-butanol, dissolve at 75 °C for 1 h to obtain a mixed solution (ergosterol is completely dissolved), cool the solution to 40 °C at a cooling rate of 6 min / °C, grow the solution for 5 h, filter at the same temperature, and rotary evaporate to dryness to obtain ergosterol in the form of flaky crystals.

[0106] The obtained ergosterol crystals were observed under an optical microscope. Fig. 9 As shown, through Fig. 9 It can be seen that the crystallization of ergosterol in n-butanol produces flaky crystals, rather than spherical crystals.

[0107] Comparative Examples 2-6

[0108] Add 1.0 g of ergosterol (ergosterol in the form of plate-like crystals) to 10 mL of tert-butanol, dissolve at 55°C for 1 hour to obtain a mixed solution (ergosterol is completely dissolved), cool the solution to 45°C at a cooling rate of 6 min / °C, grow the solution for 5 hours, filter at the same temperature, and rotary evaporate to dryness to obtain ergosterol in the form of needle-like crystals.

[0109] The obtained ergosterol crystals were observed under an optical microscope. Fig.10 As shown, through Fig.10 It can be seen that the crystallization of ergosterol in tert-butanol produces needle-shaped crystals, rather than spherical crystals.

[0110] Comparative Examples 2-7

[0111] Add 0.95 g of ergosterol (ergosterol in the form of flaky crystals) to 10 mL of n-pentanol, dissolve at 75 °C for 1 h to obtain a mixed solution (ergosterol is completely dissolved), cool the solution to 45 °C at a cooling rate of 6 min / °C, grow the solution for 5 h, filter at the same temperature, and rotary evaporate to dryness to obtain ergosterol in the form of flaky crystals.

[0112] The obtained ergosterol crystals were observed under an optical microscope. Fig.11 As shown, through Fig.11 It can be seen that the crystallization of ergosterol in n-pentanol produces flaky crystals rather than spherical crystals.

[0113] Comparative Examples 2-8

[0114] Add 1.2 g of ergosterol (ergosterol in the form of flaky crystals) to 10 mL of toluene, dissolve it at 80°C for 1 hour to obtain a mixed solution (ergosterol is completely dissolved), cool it to 60°C at a cooling rate of 6 min / °C, grow the crystals for 5 hours, filter it at this temperature, and rotary evaporate it to dryness to obtain ergosterol in the form of flaky crystals.

[0115] The obtained ergosterol crystals were observed under an optical microscope. Fig.12 As shown, through Fig.12 It can be seen that the crystallization of ergosterol in toluene produces flaky crystals, rather than spherical crystals.

[0116] Comparative Examples 2-9

[0117] Add 1.1 g of ergosterol (ergosterol in the form of flaky crystals) to 10 mL of acetone, dissolve at 60°C for 1 hour to obtain a mixed solution (ergosterol is completely dissolved), cool the temperature to 40°C at a cooling rate of 6 min / °C, grow the crystals for 5 hours, filter at the same temperature, and rotary evaporate to dryness to obtain ergosterol in the form of flaky crystals.

[0118] The obtained ergosterol crystals were observed under an optical microscope. Fig.13 As shown, through Fig.13 It can be seen that the crystallization of ergosterol in acetone produces flaky crystals rather than spherical crystals.

[0119] Comparative Example 3

[0120] Only the amount of ethyl acetate added in Example 1 was replaced with 30 mL and 40 mL; Comparative Example 3-1 and Comparative Example 3-2 were obtained accordingly.

[0121] The obtained ergosterol crystals were observed using a scanning electron microscope. The test results of Comparative Example 3-1 are as follows: Fig.14 As shown, the test results of Comparative Example 3-2 are as follows Fig.15 As shown. Fig.14 and Fig.15 It can be seen that after increasing the content of ethyl acetate, the crystals prepared are flaky crystals rather than spherical crystals.

[0122] The various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referenced to each other.

[0123] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing spherical crystals of ergosterol, characterized in that: The steps include: 1) heating and mixing ergosterol and ethyl acetate to obtain a mixed solution; 2) The mixed solution obtained in step 1) is cooled to a crystal growing temperature, and crystal growing is performed. After the crystal growing is completed, the mixed solution is filtered to obtain spherical crystals of ergosterol.

2. The method for preparing a spherical crystal of ergosterol according to claim 1, characterized in that: The mass volume ratio of ergosterol to ethyl acetate is 0.35 g: 2-5 mL.

3. The method for preparing a spherical crystal of ergosterol according to claim 2, characterized in that: The heating and mixing temperature is 75-80° C., and the heating and mixing time is 0.5-1 h.

4. A method for preparing spherical crystals of ergosterol according to any one of claims 1 to 3, characterized in that: The crystal growing temperature is 65-75° C., and the crystal growing time is 3-8 hours.

5. The method for preparing spherical crystal ergosterol according to claim 4, characterized in that: The filtration temperature in step 2) is the same as the crystal growing temperature.

6. The method for preparing spherical crystal ergosterol according to claim 5, characterized in that: The ergosterol in step 1) includes ergosterol in the form of plate-like crystals and / or ergosterol in the form of needle-like crystals.

7. Spherical crystal ergosterol prepared according to the preparation method according to any one of claims 1 to 6.

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